Zollinger-Ellison Syndrome
History:
This syndrome was first described in 1955 by Robert Zollinger and Edwin Ellison, surgeons at the Ohio State University.
Definition Zollinger-Ellison syndrome (ZES) is a rare condition caused by a gastrin-secreting tumour that causes hypersecretion of gastric acid leading to ulcer disease.
Pathogenesis:√ Gastrin works on stomach parietal cells causing
them to secrete more hydrogen ions into the stomach lumen. √ In addition, gastrin acts as a trophic factor for parietal cells, causing parietal cell hyperplasia. √ Thus there is an increase in the number of acidsecreting cells, and each of these cells produces acid at a higher rate. √ The increase in acidity contributes to the development of peptic ulcers in the stomach and duodenum. √ High acid levels lead to multiple ulcers in the stomach and small bowel.
Most tumors (≥80%) occur in the duodenum
and in the head of the pancreas. Frequently, multiple tumors are present. Commonly it occurs in gastrinoma triangle, also called Psaros triangle. Junction Of Cystic Duct With CBD Junction Between Head And Neck Of Pancreas Junction Between 2nd And 3rd Parts Of Duodenum
Approximately 50-60% are malignant and metastasize.
Zollinger-Ellison Syndrome There are two types of ZES: – Sporadic Form – 80% – Associated with multiple endocrine neoplasia type 1 (MEN 1). – 20%
Epidemiology
√ In the U.S. 0.1-1% of patients with duodenal ulcers have ZES. √ All races √ Male:Female 1.5:1 √ Age – diagnosis in 30s-50s √ Mean age of diagnosis approximately 40 years
Clinical Features Abdominal Pain
70%
Diarrhea
70%
Heartburn
50%
Nausea
25%
Vomiting
20%
Weight Loss
15%
Clinical Features – Ninety percent develop peptic ulcers, leading to abdominal pain. – Diarrhea is due to a) large volume of acid being produced in the stomach, b) neutralization of pancreatic bicarbonate and enzymes, c) inhibited Na and H20 reabsorption by small intestines due to low pH – Often are malnourished.
Clinical Features – If MEN 1/ZES is suspected, look for a h/o nephrolithiasis, hypercalcemia, and pituitary disorders. A FH of nephrolithiasis, hyperparathyroidism, and gastrinoma also may be present.
Diagnosis (Multi-Step Approach)
• Step 1: Check serum gastrin level. • Step 2: Perform a provocative test. (Secretin stimulation test) • Step 3: Perform Octreotide Scan. • Step 4: Stage and localize the gastrinoma. • Step 5: Determine if it is surgical disease.
Step 1: Check serum gastrin levels
oMust be fasting oSome recommend checking 3 fasting levels on different days oMost helpful if also check gastric pH to exclude secondary hypergastrinemia (pernicious anemia) oA serum gastrin level above 1000 pg/mL with a concurrent gastric pH of < 5.0 is virutally diagnostic. oMost ZES patients will have a value between 150 and 1000 pg/mL.
Step 2: Perform a provocative test – Done if serum gastrin level is non-diagnostic – Secretin Stimulation Test is test of choice. – This is done to differentiate hypergastrinemia as a result of gastrinomas from other causes of elevated gastrin levels. – Secretin stimulates gastrin release by gastrinomas, but inhibitis its release by gastric G cells (unknown mechanism) – Gastrin measurements are made pre and post secretin infusion and a rise by 200 pg/mL or more is greater than 90% sens and spec for ZES.
Step 3: Octreotide Scan – A nuclear medicine study that uses 111-Indium-penetreotide to identify “hot spots” of octreotide uptake by the gastrinoma. – The recommended initial imaging modality because it has the highest sensitivity (67%)
Step 4: Stage and localize the gastrinoma
– US – Endoscopy – CT scan – Somatostatin-receptor scintigraphy – MRI – Selective angiography
Endoscopy
Will reveal prominent mucosal folds and large amount of acid in stomach. Along with multiple gastric and duodenal ulcers.
Zollinger-Ellison Syndrome Step 5: Determine if it is surgical disease â&#x20AC;&#x201C; All patients with the sporadic form of ZollingerEllison syndrome and without any metastatic disease should be offered surgical resection of the primary tumor.
Treatment – Two goals of treatment
√Control the effects of gastrin √ Control the tumor
Treatment â&#x20AC;&#x201C; Prior to the advent of effective acid suppression therapy, the major morbidity and mortality arose from fulminant PUD. Total gastrectomy was the only effective therapy.
Treatment Medical Management: â&#x2C6;&#x161; High-dose proton pump inhibitors oOmeprazole 60 mg daily oEsomeprazole 120 mg daily oLansoprazole 45 mg daily oRabeprazole 60 mg daily
Treatment â&#x20AC;&#x201C; Surgical Treatment oOnly really effective for patients with sporadic
disease without evidence for metastasis. oUp to 1/3 can be cured surgically. oNot recommended for patients with ZES as a part of MEN1 because of the multifocal nature of the tumors.
Treatment Surgery: o Type 1 partial gastrectomy â&#x20AC;&#x201C;to remove G cells bearing area o Type 2 if tumor is small, removal of tumor can be done(enucleation) o If tumor is large , acid suppression is done by conservative method. Total gastrectomy is the last resort.
Treatment for metastatic disease is limited – Somatastatin analogs – Interferon alfa – Cytotoxic chemotherapy – Surgical resection – Hepatic arterial chemoembolization
Summary o Gastrin-producing neuroendocrine tumour, which causes o o o o
gastric acid hypersecretion and peptic ulcer disease. Can be sporadic or associated with multiple endocrine neoplasia syndrome type 1. Common presentation includes refractory peptic ulcer disease, abdominal pain, diarrhoea and gastrooesophageal disease. The main goal of treatment is control of gastric hypersecretion with proton-pump inhibitors. The most common cause of morbidity and mortality is metastatic gastrinoma.
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